Replicating Persistent Memory Key-Value Stores with Efficient RDMA Abstraction

Combining persistent memory (PM) with RDMA is a promising approach to performant replicated distributed key-value stores (KVSs). However, existing replication approaches do not work well when applied to PM KVSs: 1) Using RPC induces software queueing and execution at backups, increasing request latency; 2) Using one-sided RDMA WRITE causes many streams of small PM writes, leading to severe device-level write amplification (DLWA) on PM. In this paper, we propose Rowan, an efficient RDMA abstraction to handle replication writes in PM KVSs; it aggregates concurrent remote writes from different servers, and lands these writes to PM in a sequential (thus low DLWA) and one-sided (thus low latency) manner. We realize Rowan with off-the-shelf RDMA NICs. Further, we build Rowan-KV, a log-structured PM KVS using Rowan for replication. Evaluation shows that under write-intensive workloads, compared with PM KVSs using RPC and RDMA WRITE for replication, Rowan-KV boosts throughput by 1.22X and 1.39X as well as lowers median PUT latency by 1.77X and 2.11X, respectively, while largely eliminating DLWA.Comment: Accepted to OSDI 202

Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Bladder transitional cell carcinoma (BTCC) is the fourth most frequent neoplasia in men, clinically characterized by high recurrent rates and poor prognosis. Availability of urinary tumor biomarkers represents a convenient alternative for early detection and disease surveillance because of its direct contact with the tumor and sample accessibility.</p> <p>Results</p> <p>We tested urine samples from healthy volunteers and patients with low malignant or aggressive BTCC to identify potential biomarkers for early detection of BTCC by two-dimensional electrophoresis (2-DE) coupled with mass spectrometry (MS) and bioinformatics analysis. We observed increased expression of five proteins, including fibrinogen (Fb), lactate dehydrogenase B (LDHB), apolipoprotein-A1 (Apo-A1), clusterin (CLU) and haptoglobin (Hp), which were increased in urine samples of patients with low malignant or aggressive bladder cancer. Further analysis of urine samples of aggressive BTCC showed significant increase in Apo-A1 expression compared to low malignant BTCC. Apo-A1 level was measured quantitatively using enzyme-linked immunosorbent assay (ELISA) and was suggested to provide diagnostic utility to distinguish patients with bladder cancer from controls at 18.22 ng/ml, and distinguish patients with low malignant BTCC from patients with aggressive BTCC in two-tie grading system at 29.86 ng/ml respectively. Further validation assay showed that Apo-A1 could be used as a biomarker to diagnosis BTCC with a sensitivity and specificity of 91.6% and 85.7% respectively, and classify BTCC in two-tie grading system with a sensitivity and specificity of 83.7% and 89.7% respectively.</p> <p>Conclusion</p> <p>Taken together, our findings suggest Apo-A1 could be a potential biomarker related with early diagnosis and classification in two-tie grading system for bladder cancer.</p

UPPRESSO: Untraceable and Unlinkable Privacy-PREserving Single Sign-On Services

Single sign-on (SSO) allows a user to maintain only the credential at the identity provider (IdP), to login to numerous RPs. However, SSO introduces extra privacy threats, compared with traditional authentication mechanisms, as (a) the IdP could track all RPs which a user is visiting, and (b) collusive RPs could learn a user's online profile by linking his identities across these RPs. This paper proposes a privacypreserving SSO system, called UPPRESSO, to protect a user's login activities against both the curious IdP and collusive RPs. We analyze the identity dilemma between the security requirements and these privacy concerns, and convert the SSO privacy problems into an identity transformation challenge. In each login instance, an ephemeral pseudo-identity (denoted as PID_RP ) of the RP, is firstly negotiated between the user and the RP. PID_RP is sent to the IdP and designated in the identity token, so the IdP is not aware of the visited RP. Meanwhile, PID_RP is used by the IdP to transform the permanent user identity ID_U into an ephemeral user pseudo-identity (denoted as PID_U ) in the identity token. On receiving the identity token, the RP transforms PID_U into a permanent account (denoted as Acct) of the user, by an ephemeral trapdoor in the negotiation. Given a user, the account at each RP is unique and different from ID_U, so collusive RPs cannot link his identities across these RPs. We build the UPPRESSO prototype on top of MITREid Connect, an open-source implementation of OIDC. The extensive evaluation shows that UPPRESSO fulfills the requirements of both security and privacy and introduces reasonable overheads

Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

Summary Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness

Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies

Studying monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combine patient-derived and genetically engineered iPSCs with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene Tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural, and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS “heart on chip” tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies, and advances iPSC-based in vitro modeling of cardiomyopathy

REGγ is associated with multiple oncogenic pathways in human cancers

<p>Abstract</p> <p>Background</p> <p>Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ.</p> <p>Methods</p> <p>REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues</p> <p>Results</p> <p>Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis.</p> <p>Conclusions</p> <p>This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker.</p

Structure and Novel Functional Mechanism of Drosophila SNF in Sex-Lethal Splicing

Sans-fille (SNF) is the Drosophila homologue of mammalian general splicing factors U1A and U2B″, and it is essential in Drosophila sex determination. We found that, besides its ability to bind U1 snRNA, SNF can also bind polyuridine RNA tracts flanking the male-specific exon of the master switch gene Sex-lethal (Sxl) pre-mRNA specifically, similar to Sex-lethal protein (SXL). The polyuridine RNA binding enables SNF directly inhibit Sxl exon 3 splicing, as the dominant negative mutant SNF1621 binds U1 snRNA but not polyuridine RNA. Unlike U1A, both RNA recognition motifs (RRMs) of SNF can recognize polyuridine RNA tracts independently, even though SNF and U1A share very high sequence identity and overall structure similarity. As SNF RRM1 tends to self-associate on the opposite side of the RNA binding surface, it is possible for SNF to bridge the formation of super-complexes between two introns flanking Sxl exon 3 or between a intron and U1 snRNP, which serves the molecular basis for SNF to directly regulate Sxl splicing. Taken together, a new functional model for SNF in Drosophila sex determination is proposed. The key of the new model is that SXL and SNF function similarly in promoting Sxl male-specific exon skipping with SNF being an auxiliary or backup to SXL, and it is the combined dose of SXL and SNF governs Drosophila sex determination